DESCRIPTION (Verbatim from Applicant's Abstract): The burden of breast cancer in American women is striking. In the United States, breast cancer is the most common non-skin malignancy in women and the second leading cause of female cancer mortality. Approximately 180,000 new cases of breast cancer are diagnosed annually with some 44,000 deaths occurring per year. Despite its recognized value in detecting and characterizing breast disease, screen film mammography has important limitations. The false negative rate ranges from 5-30 percent depending on the definition of a false negative and the length of follow-up after a "normal" mammogram. Screening mammography is less sensitive in women with radiographically dense breast tissue, suffers from a high false positive rate and has other drawbacks including examinee tolerance of compression, variability in radiological interpretation, and radiation dose considerations. Breast imaging based on near infrared (NIR) light and contrast-enhanced magnetic resonance (MR) may provide ways to overcome some of the limitations of conventional breast exams by providing new information for diagnostic decision-making. In fact, a recent consensus report produced by a National Cancer Institute blue ribbon panel on the future of breast cancer research explicitly cited these techniques as promising avenues for advancing the detection and diagnosis of breast disease. While neither of these methods uses ionizing radiation, relies on oppressive levels of breast compression, or suffers from decreased sensitivity in dense breasts, NIR lacks spatial resolution and MR has limited specificity without a contrast agent and even then presents ambiguous tissue uptake/washout kinetics and morphological patterns. High resolution anatomical information available from MR may significantly improve the spatial scale on which NIR data can be generated and NIR-generated hemoglobin parameters may improve the interpretation of MR enhancement profiles. Combined NIR/MR imaging within a single exam session, though challenging, appears technically feasible and offers avenues for enhancing the information that either technique can provide alone. The overall goal for the proposed continuation of this project is to develop and explore the concept of combined NIR/MR breast imaging. The specific aims for the proposed funding period are to: (1) develop a fast, multi-spectral NIR data acquisition system based on a hybrid parallel/multiplexed PMT detection approach, (2) develop an MR-compatible breast interface for combined NIR/MR imaging, (3) develop and evaluate methods for incorporating MR information into the NIR reconstruction process, (4) evaluate and optimize combined NIR/MR spectral imaging in phantoms and freshly-excised ex-vivo breast tissues and (5) demonstrate the feasibility of combined NIR/MR breast exam delivery in a small cohort of women where this data can be evaluated in terms of information available from conventional breast imaging, contrast-enhanced MR studies and pathology analysis. By developing combined NIR/MR imaging, we hope to improve the potential of both NIR and MR breast cancer detection and characterization. More importantly, we hope to transcend the conventional paradigm of breast screening and diagnosis by contributing a new genre of functional information to forward the understanding of breast disease.